Universal Glia to Neurone Lactate Transfer in the Nervous System: Physiological Functions and Pathological Consequences

Abstract

Whilst it is universally accepted that the energy support of the brain is glucose, the form in which the glucose is taken up by neurones is the topic of intense debate. In the last few decades, the concept of lactate shuttling between glial elements and neural elements has emerged in which the glial cells glycolytically metabolise glucose/glycogen to lactate, which is shuttled to the neural elements via the extracellular fluid. The process occurs during periods of compromised glucose availability where glycogen stored in astrocytes provides lactate to the neurones, and is an integral part of the formation of learning and memory where the energy intensive process of learning requires neuronal lactate uptake provided by astrocytes. More recently sleep, myelination and motor end plate integrity have been shown to involve lactate shuttling. The sequential aspect of lactate production in the astrocyte followed by transport to the neurones is vulnerable to interruption and it is reported that such disparate pathological conditions as Alzheimer’s disease, amyotrophic lateral sclerosis, depression and schizophrenia show disrupted lactate signalling between glial cells and neurones.

From Obesity to Hippocampal Neurodegeneration: Pathogenesis and Non-Pharmacological Interventions

“…The exercise-induced lactate/MCT/SIRT1/PGC-1α/FNDC5/BDNF signaling transduction has exemplified the endocrine perspective of lactate shuttle [ 335 ]. Also, several reviews have emphasized the lactate shuttle involving in synaptic plasticity and astroglial-neuronal metabolism [ 347 , 348 , 349 , 350 , 351 ]. Lactate enters the presynaptic neurons through monocarboxylate transport 2 (MCT2) [ 352 ].…”

Warburg Effect, Glutamine, Succinate, Alanine, When Oxygen Matters

“…Lactate and succinate accumulation built up a metabolic and oxygen debt reimbursed later by mitochondrial oxidative metabolism when oxygen becomes available. This time-based relationship finds an echo in spatial organization and muscles/erythrocytes and liver (in the long range) [22,26], glial cells and neurons [27,28] or stromal and cancer cells [29] (in the short range) constitutes examples of spatially organized metabolic synergy between lactate producers and lactate consumers. Similar spatial organization with succinate appears to emerge in the retina [30].…”

l-Lactate: Food for Thoughts, Memory and Behavior

“…Accordingly, anomalies in the brain energy metabolism can result in severe pathologies or aggravate pre-existing conditions. In particular, Alzheimer’s Disease (AD), amyotrophic lateral sclerosis (ALS), depression, stress and schizophrenia show disruptive lactate signaling between astrocytes and neurons [ 93 ]. For instance, Positron Emission Tomography (PET) scans have documented reduced glucose utilization in brain regions affected by patients with Alzheimer, Parkinson and Huntington’s disease, as well as with ALS [ 94 ].…”